DESCRIPTION: A number of families (13) with fronto-temporal dementia and parkinsonism (FTDP) have been linked to the same (approx. 2 cM) region of chromosome 17q21. The clinical features of this disease include early behavioral change and motor manifestations leading to progressive memory loss and dementia. At autopsy, the patients with FTDP-17 all show fronto-temporal atrophy with neuronal cell loss, neruopil vacuolation and gliosis in both white and gray matter. Argyrophilic and/or tau positive neuronal inclusion are observed in some families. Ballooned neurons are found in all cases that have been examined to date. The overall of this study is to identify the gene for and the pathogenic mutations which cause FTDP-17. In order to perform this task the candidate region for FTDP-17 will be minimized using data from a series of FTDP-17 kindreds and the candidate region will be physically mapped in YACs and PACs. Known genes and ESTs will be mapped into the FTDP-17 region and then prioritized for study as candidates for FTDP-17. Sequence analysis of candidate genes (novel and previously identified, ie GFAP and tau) will be performed to identify mutations. Once the FTDP-17 gene has been identified the prevalence of the disease will be studied in both a prospective community-based dementia cohort in Rochester, Minnesota and in two autopsy cohorts.